Heroin addicts are known to have elevated rates of infection. This proposal is directed at determining the effect of opiates on immunocompetence. On the in vitro level, studies will examine whether opiates and opioid peptides can alter T cell responses. Opiates such as morphine, antagonists such as naloxone, and opioid peptides, such as beta-endorphin, methionine-enkephalin, and leucine-enkephalin, will be tested for their effect on T cell proliferation in cultures of rat splenocytes and thymocytes. [3H)Thymidine incorporation into DNA in the presence of T cell mitogens will be used as a measure of proliferation. Calcium influx is one of the earliest events associated with mitogen- stimulated T cell activation. Opioids will also be tested for their effect on basal and mitogen-stimulated 45 Ca 2+ uptake into lymphocytes. The binding and internalization of [125I] beta-endorphin into lymphocytes will be characterized. The ability of opiates and opioid peptides to block [125] beta endorphin binding site on lymphocytes will be compared to the beta-endorphin binding site in the central nervous system. Hemolytic plaque assays will be used to determine if opioids can alter antibody synthesis. Natural killer cytotoxicity as measured by a standard 51 Cr release assay, will determine if opioids can alter the cell-mediated killing target cells. On the in vivo level, these assays will be used to detect alterations in the immunce cell responses of morphine-dependent rats, compared with placebo-treated controls. These studies will results in a better understanding of how opiates modulate immunocompetence and may help explain why heroin addicts are very susceptible to viral infection.